The T-even bacteriophage - E. coli system will be investigated as a model system of viral invasion, viral structure and viral assembly. Recent experiments have shown that: a) polyglutamate derivatives of folic acid play a critical role in virus assembly and have also demonstrated that folic acid metabolism is controlled by the viral genome; and b) that one of the viral attachment proteins is a zinc metalloprotein. Work will be devoted to determine: 1) How viral genes control folyl polyglutamate metabolism in the infected cell; 2) How folates are used for viral assembly; 3) How three enzymes, dihydrofolate reductase, tymidylate synthetase, and a newly discovered folyl polyglutamate cleavage enzyme are used for the assembly of viral tail structure; 4) A search for unique inhibitors of viral assembly. 5) How the viral tail metalloprotein interacts with the host cell wall and aids the delivery of the viral DNA onto the host cell. It is hoped the detailed chemical knowledge gained from these studies will lead to the control of virus assembly and to new pinciples involving assembly of other virus particles, including those causing human diseases.